TY - JOUR
T1 - The RECQL helicase prevents replication fork collapse during replication stress
AU - Benedict, Bente
AU - van Bueren, Marit Ae
AU - van Gemert, Frank Pa
AU - Lieftink, Cor
AU - Guerrero Llobet, Sergi
AU - van Vugt, Marcel Atm
AU - Beijersbergen, Roderick L
AU - Te Riele, Hein
N1 - © 2020 Benedict et al.
PY - 2020/8/20
Y1 - 2020/8/20
N2 - Most tumors lack the G1/S phase checkpoint and are insensitive to antigrowth signals. Loss of G1/S control can severely perturb DNA replication as revealed by slow replication fork progression and frequent replication fork stalling. Cancer cells may thus rely on specific pathways that mitigate the deleterious consequences of replication stress. To identify vulnerabilities of cells suffering from replication stress, we performed an shRNA-based genetic screen. We report that the RECQL helicase is specifically essential in replication stress conditions and protects stalled replication forks against MRE11-dependent double strand break (DSB) formation. In line with these findings, knockdown of RECQL in different cancer cells increased the level of DNA DSBs. Thus, RECQL plays a critical role in sustaining DNA synthesis under conditions of replication stress and as such may represent a target for cancer therapy.
AB - Most tumors lack the G1/S phase checkpoint and are insensitive to antigrowth signals. Loss of G1/S control can severely perturb DNA replication as revealed by slow replication fork progression and frequent replication fork stalling. Cancer cells may thus rely on specific pathways that mitigate the deleterious consequences of replication stress. To identify vulnerabilities of cells suffering from replication stress, we performed an shRNA-based genetic screen. We report that the RECQL helicase is specifically essential in replication stress conditions and protects stalled replication forks against MRE11-dependent double strand break (DSB) formation. In line with these findings, knockdown of RECQL in different cancer cells increased the level of DNA DSBs. Thus, RECQL plays a critical role in sustaining DNA synthesis under conditions of replication stress and as such may represent a target for cancer therapy.
U2 - 10.26508/lsa.202000668
DO - 10.26508/lsa.202000668
M3 - Article
C2 - 32820027
VL - 3
JO - Life science alliance
JF - Life science alliance
SN - 2575-1077
IS - 10
M1 - e202000668
ER -